作者：谢玉霞1 ，姜海兵 2 ，杨洁 1 ，刘文宁 1 ，梁铖 1 ，张静 1

单位：

1.830000 新疆维吾尔自治区乌鲁木齐市，新疆医科大学附属中医医院心血管二科　；2.830000 新疆维吾尔自治区乌鲁木齐市，新疆医科大学附属中医医院心血管四科；通信作者：姜海兵，E-mail：nextlife7@163.com

关键词：

冠心病；大鼠；线粒体 ATP 敏感性钾离子通道开放剂；血脂；内皮损伤

Keywords：

Coronary disease；Rats；Mitochondrial ATP sensitive potassium channel opener；Blood lipid；Hyperlipidemia

CLC：

R 541.4

DOI：

DOI：10.3969/j.issn.1008-5971.2020.05.011

Funds：

新疆维吾尔自治区自然科学基金项目（2017D01C171）；新疆医科大学附属中医医院院级课题（ZYY2019ZD03）

摘要：

背景　线粒体 ATP 敏感性钾离子通道开放剂是一类扩血管药物，临床常用于治疗心脑血管疾病，但其对冠心病患者血脂代谢的影响、对血管内皮损伤的保护作用及相关机制尚不完全明确。目的　探讨线粒体 ATP 敏感性钾离子通道开放剂对冠心病大鼠血脂代谢和血管内皮损伤的影响及机制。方法　2018 年 8 月—2019 年 2 月，将 50只 6 周龄 SD 大鼠随机分为对照组、模型组、低剂量组、中剂量组、高剂量组，每组 10 只。除对照组外，其他组大鼠均喂养高脂饲料、腹腔注射垂体后叶素制备冠心病大鼠模型，低、中、高剂量组大鼠分别按照二氮嗪 3、5、7 mg/kg进行灌胃治疗，对照组、模型组大鼠均给予相同体积 0.9% 氯化钠溶液；五组大鼠均连续给药 14 d。比较五组大鼠治疗前后血脂指标〔包括总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）〕，治疗后眼球血OD 340 值及颈动脉血管内皮细胞成纤维细胞生长因子2（FGF-2）、血管内皮生长因子（VEGF）相对表达量。结果　治疗前模型组及低、中、高剂量组大鼠 TC、TG、LDL-C 水平高于对照组（P<0.05）；治疗前五组大鼠 HDL-C水平比较，差异无统计学意义（P>0.05）；治疗后模型组及低、中、高剂量组大鼠 TC、TG、LDL-C 水平高于对照组，低、中、高剂量组大鼠 TC、TG、LDL-C 水平低于模型组，中、高剂量组大鼠 TC、TG、LDL-C 水平低于低剂量组，高剂量组大鼠 TC、TG、LDL-C 水平低于中剂量组（P<0.05）；治疗后五组大鼠 HDL-C 水平比较，差异无统计学意义（P>0.05）。治疗后模型组大鼠眼球血 OD 340 值低于对照组，中、高剂量组大鼠眼球血 OD 340 值高于对照组，低、中、高剂量组大鼠眼球血 OD 340 值高于模型组（P<0.05）。治疗后模型组及低、中剂量组大鼠颈动脉血管内皮细胞 FGF-2及 VEGF 相对表达量高于对照组，低、中、高剂量组大鼠颈动脉血管内皮细胞 FGF-2 及 VEGF 相对表达量低于模型组（P<0.05）。结论　线粒体 ATP 敏感性钾离子通道开放剂可通过抑制羟甲基戊二酰辅酶 A（HMG-CoA）还原酶活性而改善冠心病大鼠血脂代谢，并可通过下调颈动脉血管内皮细胞 FGF-2 及 VEGF 的表达量而减轻血管内皮损伤。

Abstract：

Background　Mitochondrial ATP-sensitive potassium channel openers，as a kind of vasodilators，is commonly used in the clinical treatment of cardiovascular and cerebrovascular diseases，however its impact and relatedmechanism on blood lipid metabolism and vascular endothelial injury in patients with coronary heart disease are not yet clear.Objective　To investigate the impact and related mechanism of mitochondrial ATP-sensitive potassium channel openers onblood lipid metabolism and vascular endothelial injury in rats with coronary heart disease. Methods　From August 2018 toFebruary 2019，a total of 50 6-week-old SD rats were randomly divided into control group，model group，low-dose group，medium-dose group and high-dose group，with 10 cases in each group. Rats in model group，low-dose group，medium-dosegroup and high-dose group were fed with high-fat diet and intraperitoneal injection of pituitrin to prepare the models of coronaryheart disease，moreover rats in low-dose group，medium-dose group and high-dose group were given intragastric administrationof low-dose（3 mg/kg），medium-dose（5 mg/kg）and high-dose（7 mg/kg）diazoxide for 14 days，respectively，whilerats in control group and model group were given 0.9% sodium chloride solution with same volume for 14 days. The bloodlipid parameters（including TC，TG，LDL-C，HDL-C）before and after treatment，eyeball blood OD 340 value，relativeexpression quantity of FGF-2 and VEGF of carotid vascular endothelial cells after treatment were compared in the five groups.Results　TC，TG and LDL-C in model group，low-dose group，medium-dose group and high-dose group were statisticallysignificantly higher than those in control group before treatment（P<0.05）； there was no statistically significant differencein HDL-C in the five groups before treatment（P>0.05）； after treatment，TC，TG and LDL-C in model group，low-dosegroup，medium-dose group and high-dose group were statistically significantly higher than those in control group，TC，TGand LDL-C in low-dose group，medium-dose group and high-dose group were statistically significantly lower than those inmodel group，TC，TG and LDL-C in medium-dose group and high-dose group were statistically significantly lower than thosein low-dose group，TC，TG and LDL-C in high-dose group were statistically significantly lower than those in medium-dosegroup（P<0.05）；but there was no statistically significant difference in HDL-C in the five groups after treatment（P>0.05）.After treatment，eyeball blood OD 340 value in model group was statistically significantly lower than that in control group，eyeball blood OD 340 value in medium-dose group and high-dose group was statistically significantly higher than that in modelgroup，respectively，eyeball blood OD 340 value in low-dose group，medium-dose group and high-dose group was statisticallysignificantly higher than that in model group，respectively（P<0.05）.After treatment，relative expression quantity of FGF-2 and VEGF of carotid vascular endothelial cells in model group，low-dose group and medium-dose group was statisticallysignificantly higher than that in control group，respectively，meanwhile relative expression quantity of FGF-2 and VEGF ofcarotid vascular endothelial cells in low-dose group，medium-dose group and high-dose group was statistically significantlylower than that in model group，respectively（P<0.05）. Conclusion　Mitochondrial ATP-sensitive potassium channelopeners can improve the blood lipid metabolism through inhibition of the reductase activity of HMG-CoA in rats with coronaryheart disease，as well as reduce the vascular endothelial injury through down-regulating the expressions of FGF-2 and VEGF ofcarotid vascular endothelial cells.

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